Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Halloran, Margaret M.; Carley, William W.; Polverini, Peter J.; Haskell, Catherine J.; Phan, Stacie; Anderson, Byron; Woods, James M.; Campbell, Phillip L.; Volin, Michael V.; Bäcker, Annika E.; Koch, Alisa E.

doi:10.4049/jimmunol.164.9.4868

Cited by 62 publications

(41 citation statements)

References 33 publications

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“…Similar aberrant expression of blood group type 2 antigens, Le y /H, in vascular endothelial cells in inflammatory disease was reported, in which Le y /H antigen expression was rapidly induced by immune modulators, cytokines, lipopolysaccharide, phorbol-12-myristate-13-acetate, calcium ionophore, thrombin, histamine, and growth factors (Koch et al 1994;Halloran et al 2000). Enhanced expression of Le y /H antigens was observed in diseased skin tissues such as psoriatic skin, which was quite similar to the A type 3 antigen expression pattern.…”

Section: Discussionsupporting

confidence: 59%

Aberrant Expression of Histo-blood Group A Type 3 Antigens in Vascular Endothelial Cells in Inflammatory Sites

Nosaka

Ishida

Tanaka

et al. 2007

J Histochem Cytochem.

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Histo-blood group ABH antigens are widely distributed in human tissues. The epitopes of ABH antigens are carried by at least four different peripheral core isotypes of internal carbohydrate backbones (type 1–4). Each type of ABH antigen is expressed tissue specifically, and aberrant expression of ABH antigens is often observed during oncogenesis. We immunohistochemically examined the expression of A type 3 antigens in wounded and diseased skin tissues (A and AB blood groups). In uninjured skin, the expression of A type 3 antigens was restricted to the eccrine sweat gland. In addition to the sweat glands, A type 3 antigens were found in vascular endothelial cells of the wound sites. The extent of A type 3 antigens expression related to postinfliction intervals. A significantly higher expression rate of A type 3 antigens in endothelial cells was also observed in diseased skin, suggesting that inflammation might induce A type 3 antigen expression in endothelial cells. Double-color immunofluorescence staining of the specimens showed that von Willebrand factor (vWF) was a core-protein of A type 3 determinants aberrantly expressed in endothelial cells in inflamed tissues, suggesting that aberrant expression of A type 3 antigens is involved in stabilization of vWF in inflammation.

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Section: Discussionsupporting

confidence: 59%

Aberrant Expression of Histo-blood Group A Type 3 Antigens in Vascular Endothelial Cells in Inflammatory Sites

Nosaka

Ishida

Tanaka

et al. 2007

J Histochem Cytochem.

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“…In another in vivo investigation, increased Le y expression has been found on vascular endothelium from patients with rheumatoid arthritis where Le y was cytokine inducible. 20 These results certainly identify the significance of Le y in vascular inflammation. It is more interesting to notice that the result of tissue Western blot showed several increasing bands in vessels after ligation ( Figure 6A), indicating that there are some specific molecules carrying Le y that are induced in the injured vasculature and probably involve in leukocyte adhesion.…”

mentioning

confidence: 81%

“…13,17,18 Meanwhile, recent studies have demonstrated that Le y is upregulated in synovial endothelium and joint fluid in rheumatoid arthritis. 19,20 Le y is also found to be expressed on intercellular adhesion molecule-2 (ICAM-2) on endothelial cells. ICAM-2 is a ligand of dendritic cell-specific C-type lectin, dendritic cell-specific ICAM-3-grabbing nonintegrin.…”

mentioning

confidence: 99%

Recombinant Lectin-Like Domain of Thrombomodulin Suppresses Vascular Inflammation by Reducing Leukocyte Recruitment via Interacting With Lewis Y on Endothelial Cells

Lin

Chang

Shi

et al. 2013

ATVB

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Lin et al TM Lectin-Like Domain and Le y in Inflammation 2367recombinant TMD1 (rTMD1) has been shown to attenuate inflammation by inhibiting complement activation 8 and sequestering high mobility group box B1 protein. 9 However, except for high mobility group box B1, other interacting molecules of TMD1 that may participate in anti-inflammation are still unknown.Previously, we demonstrated that Lewis Y (Le y ; Fucα1-2Galβ1-4(Fucα1-3)GlcNAcβ1-R) is a specific carbohydrate ligand of rTMD1. 10,11 Le y is known to be highly expressed in epithelial cells, especially in cancer tissues, 12 where Le y mediates cell adhesion, 13,14 proliferation, 15,16 and apoptosis. 13,17,18 Meanwhile, recent studies have demonstrated that Le y is upregulated in synovial endothelium and joint fluid in rheumatoid arthritis. 19,20 Le y is also found to be expressed on intercellular adhesion molecule-2 (ICAM-2) on endothelial cells. ICAM-2 is a ligand of dendritic cell-specific C-type lectin, dendritic cell-specific ICAM-3-grabbing nonintegrin. The interaction of dendritic cell-specific ICAM-3-grabbing nonintegrin with ICAM-2 on vascular endothelium is Le y dependent and is essential for dendritic cell-specific ICAM-3-grabbing nonintegrin recruitment into tissues to mediate immune responses. 21,22 These findings suggest that interaction of Le y with lectin-containing receptor might be involved in recruitment of leukocytes in inflammatory responses. Because Le y is a specific ligand of rTMD1, we hypothesize that rTMD1/ Le y interaction on endothelial cells would influence leukocyte recruitment, thereby suppressing inflammation.To test our hypothesis, we examined the expression and function of Le y in endothelial cells under inflammatory conditions and studied the effect of rTMD1/Le y binding on anti-inflammation in vitro and in vivo. We discovered that leukocyte recruitment was interfered by rTMD1/Le y interaction. Animal inflammation models of thioglycollate-induced peritonitis, carotid ligation injury, and atherosclerosis were applied to further evidence the protective effect of rTMD1. On the basis of these findings, we provide a novel mechanism that rTMD1 decreases leukocyte recruitment by binding to Le y and may further attenuate inflammatory responses. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Le y Mediates Leukocyte Adhesion on InflammationTo investigate the role of Le y in inflammation, we initially tested whether Le y expression in endothelial cells would be induced by stimulation of the proinflammatory cytokine, tumor necrosis factor-α (TNF-α). As shown in Figure 1A, mRNA levels of fucosyltransferase 1 (FUT)1, FUT2, and FUT4 for Le y synthesis 23 in endothelial cells were measured. The expression of FUT4 and FUT1 was significantly increased after TNF-α stimulation for 12 and 24 hours, respectively; meanwhile, no significant difference was found in the expression of FUT2. In addition, higher Le y expression on the surface of endothelial cells was observed using flow cytometry and...

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“…Hypervascularity and hypercoagulability are typical characteristics of RCC and play significant roles in tumor proliferation and metastasis [22]. In the non-O blood group, deletion of A or B antigens induces up-regulation of precursor H and Lewis y expression, and both precursors exert angiogenic effects [23]. Also, the ABO group is a major determinant of plasma levels of von Willebrand factor (vWF) and factor VIII [24], which are detected in the endothelial cells of RCC [25].…”

Section: Discussionmentioning

confidence: 99%

ABO blood group and risk of renal cell cancer.

Cho

Joh

Choueiri

2012

JCO

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Background-The genetic determinants of sporadic renal cell cancer (RCC) are largely unknown. Previous studies have suggested associations between ABO blood group and risk of various cancers. However, its relationship to RCC remains unclear and no prospective data are available.Methods-We prospectively followed up 77,242 women in the Nurses' Health Study and 30,071 men in the Health Professionals Follow-Up Study from 1996 to 2008. The information on the ABO blood group was collected from participants' self-reports in 1996. Incidence of pathologyconfirmed RCC was compared using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards models.Results-During 12 years of follow-up, 163 cases of incident RCC were documented in women and 88 cases in men. The multivariate HRs between non-O blood group (combined group of A, AB, and B) vs. blood group O were 1.51 (95% CI 1.09-2.09) in women, 1.08 (95% CI 0.70-1.66) in men, and 1.32 (95% CI 0.95-1.82) in the pooled cohorts. The associations between ABO blood group and RCC were consistent across strata of known risk factors for RCC including age, obesity, smoking, and history of hypertension (Pinteraction ≥0.32).Conclusions-We found a suggestive non-significant association between non-O blood group and increased risk of RCC in the pooled cohorts of men and women, and this association was significant in women. Our findings need to be replicated by other prospective studies.

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Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Cited by 62 publications

References 33 publications

Aberrant Expression of Histo-blood Group A Type 3 Antigens in Vascular Endothelial Cells in Inflammatory Sites

Aberrant Expression of Histo-blood Group A Type 3 Antigens in Vascular Endothelial Cells in Inflammatory Sites

Recombinant Lectin-Like Domain of Thrombomodulin Suppresses Vascular Inflammation by Reducing Leukocyte Recruitment via Interacting With Lewis Y on Endothelial Cells

ABO blood group and risk of renal cell cancer.

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